Balaraman Kaluvu, Wolf Christian
Department of Chemistry, Georgetown University, Washington, DC 20057, USA.
Sci Adv. 2022 May 27;8(21):eabn7819. doi: 10.1126/sciadv.abn7819.
The widespread use of fluorinated organic compounds in the health, agrochemical, and materials sciences is sustained by a steadily growing pool of commercially available fine chemicals. The synthetic utility of the increasingly ubiquitous Csp─F bond, however, remains to be fully exploited, which is often a difficult task because of its paramount stability and chemical inertness. Here, we demonstrate chemodivergent activation of monofluoroalkyl compounds toward either nucleophilic or electrophilic intermediates. This is accomplished under conditions that are compatible with several reaction types and many functional groups, which drastically widens the current scope of organofluorine chemistry and sets the stage for carbon-carbon and carbon-heteroatom bond formations, stereoselective construction of bisoxindole alkaloid scaffolds via in situ Umpolung, and cross-electrophilic coupling methodology. The selective generation of either nucleophilic or electrophilic species and the possibility of doing so simultaneously or, alternatively, switching molecular polarity enable previously unidentified synthetic opportunities that recognize alkyl fluorides as chemodivergent building blocks.
市售精细化学品数量的稳步增长，支撑了含氟有机化合物在健康、农用化学品和材料科学领域的广泛应用。然而，日益普遍的Csp─F键的合成效用仍有待充分开发，由于其极高的稳定性和化学惰性，这往往是一项艰巨的任务。在此，我们展示了单氟烷基化合物向亲核或亲电中间体的化学发散活化。这是在与多种反应类型和许多官能团兼容的条件下实现的，极大地拓宽了当前有机氟化学的范围，并为碳-碳和碳-杂原子键的形成、通过原位极性翻转立体选择性构建双吲哚啉生物碱骨架以及交叉亲电偶联方法奠定了基础。亲核或亲电物种的选择性生成，以及同时进行或切换分子极性的可能性，带来了以前未被认识到的合成机会，将烷基氟化物视为化学发散性的构建单元。
